This invention was made in part with the support of the Federal government, which has rights in the invention.
This invention relates to diagnosis and treatment of ulcerative colitis.
Ulcerative colitis is a recurrent acute inflammatory disease of the large intestine. Part or all of the large intestine may be involved, although the target of the pathogenic process is the colonic epithelium and primary tissue injury usually is confined to the colonic mucosa. Involvement may extend to the rectum, and infrequently crosses the ileocecal valve into the terminal ileum.
Typically the disease is progressive, characterized by episodes of exacerbation and remission. Generally the clinical course is more severe when the disease first appears early in the patient's life and when the early symptoms are severe. The prognosis is poorer when the extent of the involvement is greater, and is generally more favorable when only the sigmoid colon and the rectum are involved.
The etiology of ulcerative colitis is unknown. A number of studies have suggested that components of the immune system may mediate or contribute to injury observed in the colonic mucosa, but it remains unclear what initiates the pathogenic processes. It has been suggested that a primary abnormality of the immune system and its regulation might serve as primary initiating factors, or that the disease process might be initiated by an infectious agent and the injury then perpetuated through immune-mediated or other processes. Although the mucosal injury observed during episodes of acute disease can resemble the effects of any of a number of recognized infectious agents, no transmissible infectious agent has been consistently identified with ulcerative colitis. Alternatively, it has been suggested that aberrant structures in the colonic mucosa might increase susceptibility of the colonic mucosa to a lumenal factor, predisposing the colonic mucosa to injury by causing a defect in the mucosal barrier or initiating inappropriate activation of injurious immune-mediated processes.
Longstanding ulcerative colitis is generally recognized as a precancerous lesion, and a finite percentage of those affected with ulcerative colitis develop colonic adenocarcinoma, usually after a disease course of ten years or more.
Thus it can be desirable to be able to detect ulcerative colitis early in the patient's life, and to be able to distinguish ulcerative colitis from other intestinal inflammations, including other inflammatory diseases such as ischemic colitis and Crohn's disease and functional disorders such as irritable bowel syndrome. Early intervention can improve the long range prognosis for the patient having ulcerative colitis. Familial studies have suggested that a genetic factor may be involved in ulcerative colitis, and specific detection of the disease in prospective parents can be useful in genetic counseling.
A number of studies, including some employing specialized histochemical staining techniques, lectin probes, or direct characterization of glycoprotein heterogeneity in colonic mucosa, have suggested that glycoconjugates in the colonic mucosa are altered in patients having ulcerative colitis.